Induction of cell cycle arrest, DNA damage, and apoptosis by nimbolide in human renal cell carcinoma cells

Hsieh, Yi‐Hsien; Lee, Chien-Hsing; Chen, Hsiao-Yun; Hsieh, Shu-Ching; Lin, Chia‐Liang; Tsai, Jen-Pi

doi:10.1007/s13277-015-3477-0

Cited by 24 publications

(24 citation statements)

References 36 publications

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“…Studies have reported that nimbolide treatment results in G2/M arrest in human renal carcinoma (786‐O and A‐498) cell lines . Sophia et al stated that nimbolide treatment induces G1/S arrest .…”

Section: Discussionmentioning

confidence: 99%

“…The antitumor activity of nimbolide has been extensively studied . Studies have reported increased activities of caspase‐3 and −9 and PARP and decreased expression of procaspase‐8 in nimbolide‐treated 786‐O and A‐498 cells . Liu et al determined that nimbolide treatment activates caspase‐3 and −9 and PARP .…”

Section: Discussionmentioning

confidence: 99%

“…Studies have reported that nimbolide treatment results in G2/M arrest in human renal carcinoma (786-O and A-498) cell lines. 42 Sophia et al stated that nimbolide treatment induces G1/S arrest. 43 In this study, the flow cytometric analysis of PI-stained cells revealed that the nimbolide treatment (4 lm) of HONE-1 cells with induces marked cell accumulation in G2/M and sub-G1 phases (Figure 2A).…”

Section: Nimbolide-induced Apoptosis Through Erk1/2 Reductionmentioning

confidence: 99%

“…25,45,46 Studies have reported increased activities of caspase-3 and 29 and PARP and decreased expression of procaspase-8 in nimbolidetreated 786-O and A-498 cells. 42 Liu et al determined that nimbolide treatment activates caspase-3 and 29 and PARP. 25 In the present study, nimbolide caused a marked dose-dependent increase in the level of cleaved caspase-3, 28, and 9 and PARP ( Figure 3).…”

Section: Nimbolide-induced Apoptosis Through Erk1/2 Reductionmentioning

confidence: 99%

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Nimbolide induces apoptosis in human nasopharyngeal cancer cells

Chien

Hsu

Lin

et al. 2017

Environmental Toxicology

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Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required. Nimbolide, derived from Azadirachta indica, has a wide range of beneficial effects, including anti-inflammatory and anticancer properties. The present study evaluated the antitumor activity of nimbolide in NPC cells and its underlying mechanisms. Our results revealed that the treatment of HONE-1 cells with nimbolide potently inhibited cell viability. Moreover, nimbolide led to cell cycle arrest, which subsequently activated caspase-3, -8, and -9 and poly (ADP-ribose) polymerase to induce cell apoptosis. Moreover, nimbolide induced Bik, Bax, and t-Bid expression in HONE-1 cells. The results indicated that nimbolide induces apoptosis through the modulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways. Nimbolide induces apoptosis in human NPC cells and is a potential chemopreventive agent against NPC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2085-2092, 2017.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Nimbolide-induced Apoptosis Through Erk1/2 Reductionmentioning

confidence: 99%

Section: Nimbolide-induced Apoptosis Through Erk1/2 Reductionmentioning

confidence: 99%

See 2 more Smart Citations

Nimbolide induces apoptosis in human nasopharyngeal cancer cells

Chien

Hsu

Lin

et al. 2017

Environmental Toxicology

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“…We recently found that nimbolide, a tetranortriterpenoid isolated from the leaves and flowers of the neem tree (Azadirachta indica), can inhibit the growth of RCC [7]. α-mangostin (Fig.…”

Section: Introductionmentioning

confidence: 99%

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

Chen

Hsieh

Lin

et al. 2017

Cell Physiol Biochem

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Background/Aims: α-mangostin has anti-carcinogenic effects against several cancers. We investigated the molecular mechanism of this compound on the metastasis of human renal carcinoma cells. Methods: Cell viability was measured using the MTT assay, and cell cycle distribution using flow cytometry. A Matrigel-based assay was used to measure in vitro cell migration and invasion. MAPK-related proteins and matrix metalloproteinase (MMP)-9 and MMP-2 expression were measured by western blotting, and MMP2/-9 activities were determined by gelatin zymography. RT-qPCR and a luciferase assay were used to examine the transcriptional activity of MMP-9. Results: α-mangostin inhibited the migration and invasion of RCC cells in a dose-dependent manner, but had no evident cytotoxic effects. Treatment of 786-O cells with α-mangostin inhibited activation of MEK and ERK. Treatment with a specific MEK inhibitor (U0126) enhanced the inhibitory effects of α-mangostin on cell migration and invasion, and the phosphorylation of ERK and MEK. Moreover, α-mangostin inhibited the expression of the MMP-9 mRNA levels as well as the activity of MMP-9 promoter, and these suppressive effects were further enhanced by U0126. Conclusions: Our results suggest that α-mangostin suppresses cell migration and invasion via MEK/ERK/MMP9 pathway, and might be a promising anti-metastatic agent against human renal cell carcinoma.

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Limonoids from neem (Azadirachta indica A. Juss.) are potential anticancer drug candidates

Nagini,

Palrasu,

Bishayee

2023

Medicinal Research Reviews

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Neem (Azadirachta indica A. Juss.), a versatile evergreen tree recognized for its ethnopharmacological value, is a rich source of limonoids of the triterpenoid class, endowed with potent medicinal properties. Extracts of neem have been documented to display anticancer effects in diverse malignant cell lines as well as in preclinical animal models that has largely been attributed to the constituent limonoids. Of late, neem limonoids have become the cynosure of research attention as potential candidate agents for cancer prevention and therapy. Among the various limonoids found in neem, azadirachtin, epoxyazadiradione, gedunin, and nimbolide, have been extensively investigated for anticancer activity. Azadirachtin, a potent biodegradable pesticide, exhibits profound antiproliferative effects by preventing mitotic spindle formation and cell division. The antiproliferative activity of gedunin has been demonstrated to be mediated primarily via inhibition of heat shock protein90 and its client proteins. Epoxyazadiradione inhibits pro‐inflammatory and kinase‐driven signaling pathways to block tumorigenesis. Nimbolide, the most potent cytotoxic neem limonoid, inhibits the growth of cancer cells by regulating the phosphorylation of keystone kinases that drive oncogenic signaling besides modulating the epigenome. There is overwhelming evidence to indicate that neem limonoids exert anticancer effects by preventing the acquisition of hallmark traits of cancer, such as cell proliferation, apoptosis evasion, inflammation, invasion, angiogenesis, and drug resistance. Neem limonoids are value additions to the armamentarium of natural compounds that target aberrant oncogenic signaling to inhibit cancer development and progression.

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Induction of cell cycle arrest, DNA damage, and apoptosis by nimbolide in human renal cell carcinoma cells

Cited by 24 publications

References 36 publications

Nimbolide induces apoptosis in human nasopharyngeal cancer cells

Nimbolide induces apoptosis in human nasopharyngeal cancer cells

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

Limonoids from neem (Azadirachta indica A. Juss.) are potential anticancer drug candidates

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